High circulating dipeptidyl peptidase 3 predicts mortality and need for organ support in cardiogenic shock: An ancillary analysis of the ACCOST-HH trial.

BACKGROUND: Cardiogenic shock is burdened with high mortality. Efforts to improve outcome are hampered by the difficulty of individual risk stratification and the lack of targetable pathways. Previous studies demonstrated that elevated circulating dipeptidyl peptidase 3 (cDPP3) is an early predictor of short-term outcome in cardiogenic shock, mostly of ischemic origin. Our objective was to investigate the association between cDPP3 and short-terms outcomes in a diverse population of cardiogenic shock. METHODS: cDPP3 was measured at baseline and after 72 hours in the ACCOST-HH trial. The association of cDPP3 with 30-day mortality and need for organ support was assessed. RESULTS: Median cDPP3 concentration at baseline was 43.2 ng/mL [21.2-74] and 77 out of the 150 patients (52%) had high cDPP3 over the pre-defined cutoff of 40 ng/mL. Elevated cDPP3 was associated with higher 30-day mortality (adjusted (a) HR=1.7 [1.0-2.9]), fewer days alive without cardiovascular support (3 [0-24] vs 21 days [5-26], p<0.0001), a higher need for renal replacement therapy (56 vs 22%, p<0.0001) and mechanical ventilation (90 vs 74%, p=0.04). Patients with sustained high cDPP3 had poor prognosis (reference group). In contrast, patients with initially high but decreasing cDPP3 at 72 hours had markedly reduced 30-day mortality (aHR=0.17 [0.084-0.34]), comparable to patients with sustained low cDPP3 (aHR=0.23 [0.12-0.41]). Need for organ support was markedly reduced in subpopulations with sustained low or decreasing cDPP3. CONCLUSION: The present study confirms the prognostic value of cDPP3 in a contemporary population of cardiogenic shock.

Mortality in patients with septic cardiomyopathy identified by longitudinal strain by speckle tracking echocardiography: An updated systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Septic cardiomyopathy is associated with poor outcomes but its definition remains unclear. In a previous meta-analysis, left ventricular (LV) longitudinal strain (LS) showed significant prognostic value in septic patients, but findings were not robust due to a limited number of studies, differences in effect size and no adjustment for confounders. METHODS: We conducted an updated systematic review (PubMed and Scopus up to 14.02.2023) and meta-analysis to investigate the association between LS and survival in septic patients. We included studies reporting global (from three apical views) or regional LS (one or two apical windows). A secondary analysis evaluated the association between LV ejection fraction (EF) and survival using data from the selected studies. RESULTS: We included fourteen studies (1678 patients, survival 69.6%) and demonstrated an association between better performance (more negative LS) and survival with a mean difference (MD) of -1.45%[-2.10, -0.80] (p < 0.0001;I2 = 42%). No subgroup differences were found stratifying studies according to number of views used to calculate LS (p = 0.31;I2 = 16%), severity of sepsis (p = 0.42;I2 = 0%), and sepsis criteria (p = 0.59;I2 = 0%). Trial sequential analysis and sensitivity analyses confirmed the primary findings. Grade of evidence was low. In the included studies, thirteen reported LVEF and we found an association between higher LVEF and survival (MD = 2.44% [0.44,4.45]; p = 0.02;I2 = 42%). CONCLUSIONS: We confirmed that more negative LS values are associated with higher survival in septic patients. The clinical relevance of this difference and whether the use of LS may improve understanding of septic cardiomyopathy and prognostication deserve further investigation. The association found between LVEF and survival is of unlikely clinical meaning. REGISTRATION: PROSPERO number CRD42023432354.

Neutralization of extracellular histones by sodium-Β-O-methyl cellobioside sulfate in septic shock.

BACKGROUND: Extracellular histones have been associated with severity and outcome in sepsis. The aim of the present study was to assess the effects of sodium-ß-O-Methyl cellobioside sulfate (mCBS), a histone-neutralizing polyanion, on the severity and outcome of sepsis in an experimental model. METHODS: This randomized placebo-controlled experimental study was performed in 24 mechanically ventilated female sheep. Sepsis was induced by fecal peritonitis. Animals were randomized to three groups: control, early treatment, and late treatment (n = 8 each). mCBS was given as a bolus (1 mg/kg) followed by a continuous infusion (1 mg/kg/h) just after sepsis induction in the early treatment group, and 4 h later in the late treatment group. Fluid administration and antimicrobial therapy were initiated 4 h T4 after feces injection, peritoneal lavage performed, and a norepinephrine infusion titrated to maintain mean arterial pressure (MAP) between 65-75 mmHg. The experiment was blinded and lasted maximum 24 h. RESULTS: During the first 4 h, MAP remained > 65 mmHg in the early treatment group but decreased significantly in the others (p < 0.01 for interaction, median value at T4: (79 [70-90] mmHg for early treatment, 57 [70-90] mmHg for late treatment, and 55 [49-60] mmHg for the control group). mCBS-treated animals required significantly less norepinephrine to maintain MAP than controls (p < 0.01 for interaction) and had lower creatinine (p < 0.01), lactate (p < 0.01), and interleukin-6 (p < 0.01) levels, associated with reduced changes in H3.1 nucleosome levels (p = 0.02). Early treatment was associated with lower norepinephrine requirements than later treatment. Two control animals died; all the mCBS-treated animals survived. CONCLUSIONS: Neutralization of extracellular histones with mCBS was associated with reduced norepinephrine requirements, improved tissue perfusion, less renal dysfunction, and lower circulating IL-6 in experimental septic shock and may represent a new therapeutic approach to be tested in clinical trials.

Pulse wave analysis as a tool for the evaluation of resuscitation therapy in septic shock.

Objective. Pulse wave analysis (PWA) can provide insights into cardiovascular biomechanical properties. The use of PWA in critically ill patients, such as septic shock patients, is still limited, but it can provide complementary information on the cardiovascular effects of treatment when compared to standard indices outlined in international guidelines. Previous works have highlighted how sepsis induces severe cardiovascular derangement with altered arterial blood pressure waveform morphology and how resuscitation according to standard haemodynamic targets is not able to restore the physiological functioning of the cardiovascular system. The aim of this work is to test the effectiveness of PWA in characterizing arterial waveforms obtained from a swine experiment involving polymicrobial septic shock and resuscitation with different drugs.Methods. During the experiment, morphological aortic waveform features, such as indices related to the dicrotic notch and inflection point, were extracted by means of PWA techniques. Finally, all the PWA indices were used to compute a clustering classification (mini batch K-means) of the pigs according to the different phases of the experiment. This analysis aimed to test if PWA features alone could be used to distinguish between the different responses to the administered therapies.Results. The PWA indices highlighted different cardiovascular conditions of the pigs in response to different treatments, despite the mean haemodynamic values typically used to guide therapy administration being similar in all animals. The clustering algorithm was able to distinguish between the different phases of the experiment and the different responses of the animals based on the unique information derived from the aortic PWA.Conclusion. Even when used alone, PWA indices were highly informative when assessing therapy responses in cases of septic shock.Significance. A complex pathological condition like septic shock requires extensive monitoring without neglecting important information from commonly measured signals such as arterial blood pressure. Future studies are needed to understand how individual differences in the response to therapy are associated with different cardiovascular conditions that may become specific therapy targets.

Angiotensin 1-7 in an experimental septic shock model.

BACKGROUND: Alterations in the renin-angiotensin system have been implicated in the pathophysiology of septic shock. In particular, angiotensin 1-7 (Ang-(1-7)), an anti-inflammatory heptapeptide, has been hypothesized to have beneficial effects. The aim of the present study was to test the effects of Ang-(1-7) infusion on the development and severity of septic shock. METHODS: This randomized, open-label, controlled study was performed in 14 anesthetized and mechanically ventilated sheep. Immediately after sepsis induction by bacterial peritonitis, animals received either Ang-(1-7) (n = 7) or placebo (n = 7) intravenously. Fluid resuscitation, antimicrobial therapy, and peritoneal lavage were initiated 4 h after sepsis induction. Norepinephrine administration was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg. RESULTS: There were no differences in baseline characteristics between groups. Septic shock was prevented in 6 of the 7 animals in the Ang-(1-7) group at the end of the 24-h period. Fluid balance and MAP were similar in the two groups; however, MAP was achieved with a mean norepinephrine dose of 0.4 µg/kg/min in the Ang-(1-7) group compared to 4.3 µg/kg/min in the control group. Heart rate and cardiac output index were lower in the Ang (1-7) than in the control group, as were plasma interleukin-6 levels, and creatinine levels. Platelet count and PaO2/FiO2 ratio were higher in the Ang-(1-7) group. Mean arterial lactate at the end of the experiment was 1.6 mmol/L in the Ang-(1-7) group compared to 7.4 mmol/L in the control group. CONCLUSIONS: In this experimental septic shock model, early Ang-(1-7) infusion prevented the development of septic shock, reduced norepinephrine requirements, limited interleukine-6 increase and prevented renal dysfunction.

Hepatic Peroxisome Proliferator-Activated Receptor Alpha Dysfunction in Porcine Septic Shock.

Despite decades of research, sepsis remains one of the most urgent unmet medical needs. Mechanistic investigations into sepsis have mainly focused on targeting inflammatory pathways; however, recent data indicate that sepsis should also be seen as a metabolic disease. Targeting metabolic dysregulations that take place in sepsis might uncover novel therapeutic opportunities. The role of peroxisome proliferator-activated receptor alpha (PPARɑ) in liver dysfunction during sepsis has recently been described, and restoring PPARɑ signaling has proven to be successful in mouse polymicrobial sepsis. To confirm that such therapy might be translated to septic patients, we analyzed metabolic perturbations in the liver of a porcine fecal peritonitis model. Resuscitation with fluids, vasopressor, antimicrobial therapy and abdominal lavage were applied to the pigs in order to mimic human clinical care. By using RNA-seq, we detected downregulated PPARɑ signaling in the livers of septic pigs and that reduced PPARɑ levels correlated well with disease severity. As PPARɑ regulates the expression of many genes involved in fatty acid oxidation, the reduced expression of these target genes, concomitant with increased free fatty acids in plasma and ectopic lipid deposition in the liver, was observed. The results obtained with pigs are in agreement with earlier observations seen in mice and support the potential of targeting defective PPARɑ signaling in clinical research.

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock.

BACKGROUND: Angiotensin II is one of the vasopressors available for use in septic shock. However, its effects on the septic myocardium remain unclear. The aim of the study was to compare the effects of angiotensin II and norepinephrine on cardiac function and myocardial oxygen consumption, inflammation and injury in experimental septic shock. METHODS: This randomized, open-label, controlled study was performed in 20 anesthetized and mechanically ventilated pigs. Septic shock was induced by fecal peritonitis in 16 animals, and four pigs served as shams. Resuscitation with fluids, antimicrobial therapy and abdominal drainage was initiated one hour after the onset of septic shock. Septic pigs were randomly allocated to receive one of the two drugs to maintain mean arterial pressure between 65 and 75 mmHg for 8 h. RESULTS: There were no differences in MAP, cardiac output, heart rate, fluid balance or tissue perfusion indices in the two treatment groups but myocardial oxygen consumption was greater in the norepinephrine-treated animals. Myocardial mRNA expression of interleukin-6, interleukin-6 receptor, interleukin-1 alpha, and interleukin-1 beta was higher in the norepinephrine than in the angiotensin II group. CONCLUSIONS: In septic shock, angiotensin II administration is associated with a similar level of cardiovascular resuscitation and less myocardial oxygen consumption, and inflammation compared to norepinephrine.

Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs.

Elevated circulating cardiac troponin T (cTnT) is frequent in septic shock patients. Signs of myocardial ischemia and myocyte necrosis are not universally present, but the precise mechanism for elevated cTnT is unknown. We investigated plasma and heart tissue metabolites concentration in six septic shock (SS) and three sham swine undergoing a protocol of polymicrobial septic shock and resuscitation, in order to highlight possible pathways and biomarkers involved in troponin release (high sensitive cardiac troponin T, hs-cTnT). The animals were divided into two groups: the high cTnT group (n = 3) were pigs showing a significantly higher concentration of cTnT and lactate after resuscitation; the low cTnT group (n = 6, three sham and three septic shock) characterized by a lower value of cTnT and a lactate level < 2 mmol/L. Spearman correlation was assessed on plasma fold-change of cTnT, cytokines (TNF-α and IL-10), and metabolites. Finally, the fold-change between the end of resuscitation and baseline values (Res./BL) of plasma metabolites was used to perform a partial least square discriminant analysis (PLS-DA) with three latent variables. Before building the model, the number of features was reduced by summing up the metabolites of the same class that resulted similarly correlated to cTnT fold-change. Proline and glycine were significantly higher in the high cTnT group at the end of experiment both in the myocardium and plasma analyses. Moreover, plasma proline fold-change was found to be positively correlated with cTnT and cytokine fold-changes, and trans-4-hydroxyproline (t4-OH-Pro) fold-change was positively correlated with cTnT fold-change. The PLS-DA model was able to separate the two groups and, among the first ranked features based on VIP score, we found sugars, t4-OH-Pro, proline, creatinine, total amount of sphingomyelins, and glycine. Proline, t4-OH-Pro, and glycine are very abundant in collagen, and our results may suggest that collagen degradation could represent a possible mechanism contributing to septic myocardial injury. The common phenotype of septic cardiomyopathy could be associated to dysregulated collagen metabolism and/or degradation, further exacerbated by higher inflammation and oxidative stress.

A comprehensive neuromonitoring approach in a large animal model of cardiac arrest.

BACKGROUND: Anoxic brain injuries represent the main determinant of poor outcome after cardiac arrest (CA). Large animal models have been described to investigate new treatments during CA and post-resuscitation phase, but a detailed model that includes extensive neuromonitoring is lacking. METHOD: Before an electrically-induced 10-minute CA and resuscitation, 46 adult pigs underwent neurosurgery for placement of a multifunctional probe (intracranial pressure or ICP, tissue oxygen tension or PbtO2 and cerebral temperature) and a bolt-based technique for the placement and securing of a regional blood flow probe and two sEEG electrodes; two modified cerebral microdialysis (CMD) probes were also inserted in the frontal lobes and accidental misplacement was prevented using a perforated head support. RESULT: 42 animals underwent the CA procedure and 41 achieved the return of spontaneous circulation (ROSC). In 4 cases (8.6%) an adverse event took place during preparation, but only in two cases (4.3%) this was related to the neurosurgery. In 6 animals (13.3%) the minor complications that occurred resolved after probe repositioning. CONCLUSION: Herein we provide a detailed comprehensive neuromonitoring approach in a large animal model of CA that might help future research.

Early Hyperdynamic Sepsis Alters Coronary Blood Flow Regulation in Porcine Fecal Peritonitis.

Background: Sepsis is a common condition known to impair blood flow regulation and microcirculation, which can ultimately lead to organ dysfunction but such contribution of the coronary circulation remains to be clarified. We investigated coronary blood flow regulatory mechanisms, including autoregulation, metabolic regulation, and endothelial vasodilatory response, in an experimental porcine model of early hyperdynamic sepsis. Methods: Fourteen pigs were randomized to sham (n = 7) or fecal peritonitis-induced sepsis (n = 7) procedures. At baseline, 6 and 12 h after peritonitis induction, the animals underwent general and coronary hemodynamic evaluation, including determination of autoregulatory breakpoint pressure and adenosine-induced maximal coronary vasodilation for coronary flow reserve and hyperemic microvascular resistance calculation. Endothelial-derived vasodilatory response was assessed both in vivo and ex vivo using bradykinin. Coronary arteries were sampled for pathobiological evaluation. Results: Sepsis resulted in a right shift of the autoregulatory breakpoint pressure, decreased coronary blood flow reserve and increased hyperemic microvascular resistance from the 6th h after peritonitis induction. In vivo and ex vivo endothelial vasomotor function was preserved. Sepsis increased coronary arteries expressions of nitric oxide synthases, prostaglandin I2 receptor, and prostaglandin F2α receptor. Conclusion: Autoregulation and metabolic blood flow regulation were both impaired in the coronary circulation during experimental hyperdynamic sepsis, although endothelial vasodilatory response was preserved.

Application of an Exploratory Knowledge-Discovery Pipeline Based on Machine Learning to Multi-Scale OMICS Data to Characterise Myocardial Injury in a Cohort of Patients with Septic Shock: An Observational Study.

Currently, there is no therapy targeting septic cardiomyopathy (SC), a key contributor to organ dysfunction in sepsis. In this study, we used a machine learning (ML) pipeline to explore transcriptomic, proteomic, and metabolomic data from patients with septic shock, and prospectively collected measurements of high-sensitive cardiac troponin and echocardiography. The purposes of the study were to suggest an exploratory methodology to identify and characterise the multiOMICs profile of (i) myocardial injury in patients with septic shock, and of (ii) cardiac dysfunction in patients with myocardial injury. The study included 27 adult patients admitted for septic shock. Peripheral blood samples for OMICS analysis and measurements of high-sensitive cardiac troponin T (hscTnT) were collected at two time points during the ICU stay. A ML-based study was designed and implemented to untangle the relations among the OMICS domains and the aforesaid biomarkers. The resulting ML pipeline consisted of two main experimental phases: recursive feature selection (FS) assessing the stability of biomarkers, and classification to characterise the multiOMICS profile of the target biomarkers. The application of a ML pipeline to circulate OMICS data in patients with septic shock has the potential to predict the risk of myocardial injury and the risk of cardiac dysfunction.

The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation.

In patients with chronic aortic regurgitation (AR), excessive preload and afterload increase left ventricle wall stress, leading to left ventricular systolic dysfunction. Thus, the objective of the present study was to evaluate the effects of the myosin activator omecamtiv mecarbil (OM) on left ventricle wall stress in an experimental rat model of severe chronic AR. Forty adult male Wistar rats were randomized into two experimental groups: induction of AR (acute phase) by retrograde puncture (n = 34) or a sham intervention (n = 6). Rats that survived the acute phase (n = 18) were randomized into an OM group (n = 8) or a placebo group (n = 10). Equal volumes of OM (1.2 mg/kg/h) or placebo (0.9% NaCl) were continuously infused into the femoral vein over 30 min. OM significantly decreased end-systolic and end-diastolic and maximum wall stress in this experimental rat model of chronic severe AR (p < 0.001) and increased systolic performance assessed by fractional shortening and left ventricle end-systolic diameter; both p < 0.05). These effects were correlated with decreased indices of global cardiac function (cardiac output and stroke volume; p < 0.05) but were not inferior to baseline pump indices. Infusion with placebo did not affect global cardiac function but decreased end-systolic wall stress (p < 0.05) and increased systolic performance (all p < 0.001). In the sham-operated (control) group, OM decreased diastolic wall stress (p < 0.05). Based on these results, OM had a favorable effect on left ventricle wall stress in an experimental rat model of severe chronic AR.

The autonomic nervous system in septic shock and its role as a future therapeutic target: a narrative review.

The autonomic nervous system (ANS) regulates the cardiovascular system. A growing body of experimental and clinical evidence confirms significant dysfunction of this regulation during sepsis and septic shock. Clinical guidelines do not currently include any evaluation of ANS function during the resuscitation phase of septic shock despite the fact that the severity and persistence of ANS dysfunction are correlated with worse clinical outcomes. In the critical care setting, the clinical use of ANS-related hemodynamic indices is currently limited to preliminary investigations trying to predict and anticipate imminent clinical deterioration. In this review, we discuss the evidence supporting the concept that, in septic shock, restoration of ANS-mediated control of the cardiovascular system or alleviation of the clinical consequences induced by its dysfunction (e.g., excessive tachycardia, etc.), may be an important therapeutic goal, in combination with traditional resuscitation targets. Recent studies, which have used standard and advanced monitoring methods and mathematical models to investigate the ANS-mediated mechanisms of physiological regulation, have shown the feasibility and importance of monitoring ANS hemodynamic indices at the bedside, based on the acquisition of simple signals, such as heart rate and arterial blood pressure fluctuations. During the early phase of septic shock, experimental and/or clinical studies have shown the efficacy of negative-chronotropic agents (i.e., beta-blockers or ivabradine) in controlling persistent tachycardia despite adequate resuscitation. Central α-2 agonists have been shown to prevent peripheral adrenergic receptor desensitization by reducing catecholamine exposure. Whether these new therapeutic approaches can safely improve clinical outcomes remains to be confirmed in larger clinical trials. New technological solutions are now available to non-invasively modulate ANS outflow, such as transcutaneous vagal stimulation, with initial pre-clinical studies showing promising results and paving the way for ANS modulation to be considered as a new potential therapeutic target in patients with septic shock.

Quantification of Cardiac Kinetic Energy and Its Changes During Transmural Myocardial Infarction Assessed by Multi-Dimensional Seismocardiography.

Introduction: Seismocardiography (SCG) records cardiac and blood-induced motions transmitted to the chest surface as vibratory phenomena. Evidences demonstrate that acute myocardial ischemia (AMI) profoundly affects the SCG signals. Multidimensional SCG records cardiac vibrations in linear and rotational dimensions, and scalar parameters of kinetic energy can be computed. We speculate that AMI and revascularization profoundly modify cardiac kinetic energy as recorded by SCG. Methods: Under general anesthesia, 21 swine underwent 90 min of myocardial ischemia induced by percutaneous sub-occlusion of the proximal left anterior descending (LAD) coronary artery and subsequent revascularization. Invasive hemodynamic parameters were continuously recorded. SCG was recorded during baseline, immediately and 80 min after LAD sub-occlusion, and immediately and 60 min after LAD reperfusion. iK was automatically computed for each cardiac cycle (iK CC ) in linear (iK Lin ) and rotational (iK Rot ) dimensions. iK was calculated as well during systole and diastole (iK Sys and iK Dia , respectively). Echocardiography was performed at baseline and after revascularization, and the left ventricle ejection fraction (LVEF) along with regional left ventricle (LV) wall abnormalities were evaluated. Results: Upon LAD sub-occlusion, 77% of STEMI and 24% of NSTEMI were observed. Compared to baseline, troponins increased from 13.0 (6.5; 21.3) ng/dl to 170.5 (102.5; 475.0) ng/dl, and LVEF dropped from 65.0 ± 0.0 to 30.6 ± 5.7% at the end of revascularization (both p < 0.0001). Regional LV wall abnormalities were observed as follows: anterior MI, 17.6% (three out of 17); septal MI, 5.8% (one out of 17); antero-septal MI, 47.1% (eight out of 17); and infero-septal MI, 29.4% (five out of 17). In the linear dimension, i K L i n C C , i K L i n S y s , and i K L i n D i a dropped by 43, 52, and 53%, respectively (p < 0.0001, p < 0.0001, and p = 0.03, respectively) from baseline to the end of reperfusion. In the rotational dimension, i K R o t C C and i K R o t S y s dropped by 30 and 36%, respectively (p = 0.0006 and p < 0.0001, respectively), but i K R o t D i a did not change (p = 0.41). All the hemodynamic parameters, except the pulmonary artery pulse pressure, were significantly correlated with the parameters of iK, except for the diastolic component. Conclusions: In this very context of experimental AMI with acute LV regional dysfunction and no concomitant AMI-related heart valve disease, linear and rotational iK parameters, in particular, systolic ones, provide reliable information on LV contractile dysfunction and its effects on the downstream circulation. Multidimensional SCG may provide information on the cardiac contractile status expressed in terms of iK during AMI and reperfusion. This automatic system may empower health care providers and patients to remotely monitor cardiovascular status in the near future.

An update on levosimendan in acute cardiac care: applications and recommendations for optimal efficacy and safety.

Introduction: In the 20 years since its introduction to the palette of intravenous hemodynamic therapies, the inodilator levosimendan has established itself as a valuable asset for the management of acute decompensated heart failure. Its pharmacology is notable for delivering inotropy via calcium sensitization without an increase in myocardial oxygen consumption.Areas covered: Experience with levosimendan has led to its applications expanding into perioperative hemodynamic support and various critical care settings, as well as an array of situations associated with acutely decompensated heart failure, such as right ventricular failure, cardiogenic shock with multi-organ dysfunction, and cardio-renal syndrome. Evidence suggests that levosimendan may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support and may be superior to dobutamine in terms of short-term survival, especially in patients on beta-blockers. Positive effects on kidney function have been noted, further differentiating levosimendan from catecholamines and phosphodiesterase inhibitors.Expert opinion:Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy. When attention is given to avoiding or correcting hypovolemia and hypokalemia, an early use of the drug in the treatment algorithm is preferred.

The PRICES statement: an ESICM expert consensus on methodology for conducting and reporting critical care echocardiography research studies.

PURPOSE: Echocardiography is a common tool for cardiac and hemodynamic assessments in critical care research. However, interpretation (and applications) of results and between-study comparisons are often difficult due to the lack of certain important details in the studies. PRICES (Preferred Reporting Items for Critical care Echocardiography Studies) is a project endorsed by the European Society of Intensive Care Medicine and conducted by the Echocardiography Working Group, aiming at producing recommendations for standardized reporting of critical care echocardiography (CCE) research studies. METHODS: The PRICE panel identified lists of clinical and echocardiographic parameters (the "items") deemed important in four main areas of CCE research: left ventricular systolic and diastolic functions, right ventricular function and fluid management. Each item was graded using a critical index (CI) that combined the relative importance of each item and the fraction of studies that did not report it, also taking experts' opinion into account. RESULTS: A list of items in each area that deemed essential for the proper interpretation and application of research results is recommended. Additional items which aid interpretation were also proposed. CONCLUSION: The PRICES recommendations reported in this document, as a checklist, represent an international consensus of experts as to which parameters and information should be included in the design of echocardiography research studies. PRICES recommendations provide guidance to scientists in the field of CCE with the objective of providing a recommended framework for reporting of CCE methodology and results.

Reducing tachycardia in septic shock patients: do esmolol and ivabradine have a chronotropic effect only?

An elevated heart rate (HR) often persists in resuscitated septic shock patients, increasing the risk of mortality. Several drugs for HR control, such as esmolol and ivabradine, have been tested in the recent years, but their benefit on the overall cardiovascular system is still under investigation. The aim of this study is to investigate the hemodynamic effects of the two drugs in a protocol of polymicrobial septic shock and resuscitation, mainly focusing on the vascular function. Twelve pigs were divided into three experimental groups: the esmolol-treated group (n=4), the ivabradine-treated group (n=5) and the control group (n=3). The characteristic arterial time constant τ was computed on aortic arterial pressure (AoP), together with estimates of total arterial compliance and peripheral resistance. Power spectral analysis of aortic and radial diastolic BP oscillations was performed to estimate the sympathetic autonomic control of vascular tone. Septic shock induced a severe cardiac and vascular disarray, only partially resolved by resuscitation. The administration of esmolol, but not ivabradine, was beneficial both for cardiac and vascular function, thereby its adjunction to standard therapies could help to improve patient's condition and optimize the resuscitation strategies.Clinical Relevance-This study shows a potential beneficial effect of esmolol on the arterial tree.

Tachycardia control in septic shock with esmolol and ivabradine: a comparison on heart function.

Persisting tachycardia is often observed in resuscitated septic shock patients, and it is an independent risk factor for increased mortality. Recently, several drugs, such as esmolol and ivabradine, have been proved to be beneficial in HR control, but their overall impact on cardiac functions needs further investigation. The aim of this study is to study the effects of the two drugs on heart function in a protocol of polymicrobial septic shock and resuscitation. Twelve pigs were divided into three experimental groups: the esmolol-treated group (n=4), the ivabradine-treated group (n=5) and the control group (n=3). Cardiac autonomic activity was estimated by heart rate variability (HRV) indices and baroreflex sensitivity (BRS). The Buckberg index was adopted to evaluate myocardial oxygenation efficiency. Septic shock induced a severe autonomic dysfunction and a lower cardiac efficiency, not resolved by fluids resuscitation. The administration of the drugs improved both the HRV and the BRS, but this favourable condition was preserved after noradrenaline administration only in the esmolol group. The interaction of esmolol with the autonomic system is beneficial in septic shock to restore an improved condition of HRV and control, while ivabradine is not as effective when administered in adjunction to noradrenaline.